Lipid Changes in the Aged Brain: Effect on Synaptic Function and Neuronal Survival

As the brain ages, cognitive and motor performance decline. This decline is thought to be largely due to the accumulation of damaging products from normal oxidative metabolism and to the perturbation of general body homeostasis and brain-circulation separation. Despite this abundance of insults, the aged brain contains few dead neurons, suggesting that aging must be paralleled by triggering or enhancing neuronal survival mechanisms. Recent evidence points to the contribution of changes in the lipid composition of membranes to both age-dependent cognitive decline and robust neuronal survival. In this review, we describe and discuss the current understanding of the roles of lipids in neuronal aging, with special attention to their influence on membrane fusion, neurotransmitter receptor dynamics and survival/death signaling pathways.